2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary

Transcription

1 Accepted Manuscript 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary Craig T. January, MD, PhD, FACC L. Samuel Wann, MD, MACC, FAHA Joseph S. Alpert, MD, FACC, FAHA Hugh Calkins, MD, FACC, FAHA, FHRS Joseph C. Cleveland Jr., MD, FACC Joaquin E. Cigarroa, MD, FACC Jamie B. Conti, MD, FACC, FHRS Patrick T. Ellinor, MD, PhD, FAHA Michael D. Ezekowitz, MB, ChB, FACC, FAHA Michael E. Field, MD, FACC, FHRS Katherine T. Murray, MD, FACC, FAHA, FHRS Ralph L. Sacco, MD, FAHA William G. Stevenson, MD, FACC, FAHA, FHRS Patrick J. Tchou, MD, FACC Cynthia M. Tracy, MD, FACC, FAHA Clyde W. Yancy, MD, FACC, FAHA PII: S (14) DOI: /j.jacc Reference: JAC To appear in: Journal of the American College of Cardiology Please cite this article as: January CT, Wann LS, Alpert JS, Calkins H, Cleveland Jr JC, Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW, 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary, Journal of the American College of Cardiology (2014), doi: / j.jacc This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society Developed in Collaboration With the Society of Thoracic Surgeons WRITING COMMITTEE MEMBERS* Craig T. January, MD, PhD, FACC, Chair L. Samuel Wann, MD, MACC, FAHA, Vice Chair* Joseph S. Alpert, MD, FACC, FAHA* Michael E. Field, MD, FACC, FHRS Hugh Calkins, MD, FACC, FAHA, FHRS* Katherine T. Murray, MD, FACC, FAHA, FHRS Joseph C. Cleveland, Jr, MD, FACC Ralph L. Sacco, MD, FAHA Joaquin E. Cigarroa, MD, FACC William G. Stevenson, MD, FACC, FAHA, FHRS* Jamie B. Conti, MD, FACC, FHRS* Patrick J. Tchou, MD, FACC Patrick T. Ellinor, MD, PhD, FAHA Cynthia M. Tracy, MD, FACC, FAHA Michael D. Ezekowitz, MB, ChB, FACC, FAHA* Clyde W. Yancy, MD, FACC, FAHA ACC/AHA TASK FORCE MEMBERS Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, CCNS, CCRN, FAHA Judith S. Hochman, MD, FACC, FAHA Biykem Bozkurt, MD, PhD, FACC, FAHA Richard J. Kovacs, MD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC E. Magnus Ohman, MD, FACC Mark A. Creager, MD, FACC, FAHA** Susan J. Pressler, PhD, RN, FAHA Lesley H. Curtis, PhD Frank W. Sellke, MD, FACC, FAHA David DeMets, PhD Win-Kuang Shen, MD, FACC, FAHA Robert A. Guyton, MD, FACC** William G. Stevenson, MD, FACC, FAHA** Clyde W. Yancy, MD, FACC, FAHA** *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply; see Appendix 1 for recusal information. ACC/AHA Representative. Heart Rhythm Society Representative. ACC/AHA Task Force on Performance Measures Liaison. Society of Thoracic Surgeons Representative. ACC/AHA Task Force on Practice Guidelines Liaison. **Former Task Force member during the writing effort. This document was approved by the American College of Cardiology Board of Trustees, the American Heart Association Science Advisory and Coordinating Committee, and the Heart Rhythm Society Board of Trustees in March The American College of Cardiology requests that this document be cited as follows: January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; :. This article is copublished in Circulation. Copies: This document is available on the World Wide Web sites of the American College of Cardiology ( the American Heart Association (my.americanheart.org), and the Heart Rhythm Society ( A copy of the document is available at by selecting either the By Topic link or the By Publication Date link. For copies of this document, please contact the Elsevier Inc. Reprint Department, fax (212) , reprints@elsevier.com. Page 1 of 56

3 Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Please contact 2014 by the American Heart Association, Inc., the American College of Cardiology Foundation, and the Heart Rhythm Society. Page 2 of 56

4 Table of s Preamble Introduction Methodology and Evidence Review Organization of the Writing Committee Document Review and Approval Scope of the Guideline Clinical Characteristics and Evaluation of AF AF Classification Mechanisms of AF and Pathophysiology Risk Factors and Associated Heart Disease Clinical Evaluation: Recommendation Thromboembolic Risk and Treatment Risk-Based Antithrombotic Therapy: Recommendations Risk Stratification Schemes (CHADS 2, CHA 2 DS 2 -VASc, and HAS-BLED) Considerations in Selecting Anticoagulants Cardiac Surgery LAA Occlusion/Excision: Recommendation Rate Control: Recommendations Rhythm Control Thromboembolism Prevention: Recommendations Direct-Current Cardioversion: Recommendations Pharmacological Cardioversion: Recommendations Antiarrhythmic Drugs to Maintain Sinus Rhythm: Recommendations Upstream Therapy: Recommendations AF Catheter Ablation to Maintain Sinus Rhythm: Recommendations Surgery Maze Procedures: Recommendations Specific Patient Groups and AF Hypertrophic Cardiomyopathy: Recommendations AF Complicating Acute Coronary Syndrome: Recommendations Hyperthyroidism: Recommendations Pulmonary Disease: Recommendations Wolff-Parkinson-White and Pre-Excitation Syndromes: Recommendations Heart Failure: Recommendations Familial (Genetic) AF: Recommendation Postoperative Cardiac and Thoracic Surgery: Recommendations Evidence Gaps and Future Research Directions Appendix 1. Author Relationships With Industry and Other Entities (Relevant) Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) Appendix 3. Initial Clinical Evaluation in Patients With AF References Page 3 of 56

5 Preamble The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist clinicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a foundation for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools. The American College of Cardiology (ACC) and the American Heart Association (AHA) have jointly engaged in the production of guidelines in the area of cardiovascular disease since The ACC/AHA Task Force on Practice Guidelines (Task Force), whose charge is to develop, update, or revise practice guidelines for cardiovascular diseases and procedures, directs this effort. Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop, update or revise written recommendations for clinical practice. Experts in the subject under consideration are selected from both organizations to examine subjectspecific data and write guidelines. Writing committees are specifically charged to perform a literature review, weigh the strength of evidence for or against particular tests, treatments, or procedure, and include estimates of expected health outcomes where such data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered, as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost is considered; however, review of data on efficacy and outcomes constitutes the primary basis for preparing recommendations in this guideline. In analyzing the data, and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force (1). The Classification of Recommendation (COR) is an estimate of the size of the treatment effect, with consideration given to risks versus benefits, as well as evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm; this is defined in Table 1. The Level of Evidence (LOE) is an estimate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting each recommendation, with the weight of evidence ranked as LOE A, B, or C, according to specific definitions that are included in Table 1. Studies are identified as observational, retrospective, prospective, or randomized, as appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and are ranked as LOE C. When recommendations at LOE C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current practice among the clinician members of the Page 4 of 56

6 writing committee is the basis for LOE C recommendations and no references are cited. The schema for COR and LOE is summarized in Table 1, which also provides suggested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Class III recommendations to delineate whether the recommendation is determined to be of no benefit or is associated with harm to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment or strategy versus another are included for COR I and IIa, LOE A or B only. In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy (GDMT) to represent optimal medical therapy as defined by ACC/AHA guideline (primarily Class I)-recommended therapies. This new term, GDMT, is used herein and throughout subsequent guidelines. Because the ACC/AHA practice guidelines address patient populations (and clinicians) residing in North America, drugs that are not currently available in North America are discussed in the text without a specific COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential impact of different practice patterns and patient populations on the treatment effect and relevance to the ACC/AHA target population to determine whether the findings should inform a specific recommendation. The ACC/AHA practice guidelines are intended to assist clinicians in clinical decision making by describing a range of generally acceptable approaches to the diagnosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment about care of a particular patient must be made by the clinician and patient in light of all the circumstances presented by that patient. As a result, situations may arise in which deviations from these guidelines may be appropriate. Clinical decision making should involve consideration of the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas are identified within each respective guideline when appropriate. Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, clinicians should make every effort to engage the patient s active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, benefits, and alternatives to a particular treatment and should be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, for which the benefit-to-risk ratio may be lower. Page 5 of 56

7 The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of relationships with industry and other entities (RWI) among the members of the writing committee. All writing committee members and peer reviewers of the guideline are required to disclose all current healthcare-related relationships, including those existing 12 months before initiation of the writing effort. In December 2009, the ACC and AHA implemented a new RWI policy that requires the writing committee chair plus a minimum of 50% of the writing committee to have no relevant RWI (Appendix 1 includes the ACC/AHA definition of relevance). The Task Force and all writing committee members review their respective RWI disclosures during each conference call and/or meeting of the writing committee, and members provide updates to their RWI as changes occur. All guideline recommendations require a confidential vote by the writing committee and require approval by a consensus of the voting members. Members may not draft or vote on any recommendations pertaining to their RWI. Members who recused themselves from voting are indicated in the list of writing committee members, and specific section recusals are noted in Appendix 1. Authors and peer reviewers RWI pertinent to this guideline are disclosed in Appendixes 1 and 2. In addition, to ensure complete transparency, writing committee members comprehensive disclosure information including RWI not pertinent to this document is available as an online supplement ( Comprehensive disclosure information for the Task Force is also available online at Forces.aspx. The ACC and AHA exclusively sponsor the work of the writing committee, without commercial support. Writing committee members volunteered their time for this activity. Guidelines are official policy of both the ACC and AHA. In an effort to maintain relevance at the point of care for clinicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, several changes to these guidelines will be apparent, including limited narrative text, a focus on summary and evidence tables (with references linked to abstracts in PubMed), and more liberal use of summary recommendation tables (with references that support LOE) to serve as a quick reference. In April 2011, the Institute of Medicine released 2 reports: Finding What Works in Health Care: Standards for Systematic Reviews and Clinical Practice Guidelines We Can Trust (2, 3). It is noteworthy that the Institute of Medicine cited ACC/AHA practice guidelines as being compliant with many of the proposed standards. A thorough review of these reports and of our current methodology is under way, with further enhancements anticipated. The recommendations in this guideline are considered current until they are superseded by a focused update, the full-text guideline is revised, or until a published addendum declares it out of date and no longer Page 6 of 56

8 official ACC/AHA policy. The reader is encouraged to consult the full-text guideline (4) for additional guidance and details about atrial fibrillation (AF), since the Executive Summary contains only the recommendations. Jeffrey L. Anderson, MD, FACC, FAHA Chair, ACC/AHA Task Force on Practice Guidelines A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes mellitus, history of prior myocardial infarction, history of heart failure, and prior aspirin use. For comparative-effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. Page 7 of 56

9 1. Introduction 1.1. Methodology and Evidence Review The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review, focusing on 2006 to the present, was conducted through October 2012, and selected other references through February The relevant data are included in evidence tables in the Data Supplement available online at ( Searches were extended to studies, reviews, and other evidence conducted in human subjects and that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected databases relevant to this guideline. Key search words included but were not limited to the following: age, antiarrhythmic, atrial fibrillation, atrial remodeling, atrioventricular conduction, atrioventricular node, cardioversion, classification, clinical trial, complications, concealed conduction, costeffectiveness, defibrillator, demographics, epidemiology, experimental, heart failure, hemodynamics, human, hyperthyroidism, hypothyroidism, meta-analysis, myocardial infarction, pharmacology, postoperative, pregnancy, pulmonary disease, quality of life, rate control, rhythm control, risks, sinus rhythm, symptoms, and tachycardia-mediated cardiomyopathy. Additionally, the committee reviewed documents related to the subject matter previously published by the ACC and AHA. References selected and published in this document are representative and not all-inclusive Organization of the Writing Committee The 2014 AF writing committee was composed of clinicians with broad expertise related to AF and its treatment including adult cardiology, electrophysiology, cardiothoracic surgery, and heart failure (HF); and was assisted by staff from the ACC and AHA. Under the guidance of the Task Force, the Heart Rhythm Society was invited to be a partner organization and has provided representation. The writing committee also included a representative from the Society of Thoracic Surgery. The rigorous methodological policies and procedures noted in the Preamble act to differentiate ACC/AHA guidelines from other published guidelines and statements Document Review and Approval This document was reviewed by 2 official reviewers each nominated by the ACC, the AHA, and the Heart Rhythm Society, as well as 1 reviewer from the Society of Thoracic Surgeons, and 43 individual content reviewers (from the ACC Electrophysiology Committee, Adult Congenital and Pediatric Cardiology Council, Association of International Governors, Heart Failure and Transplant Council, Imaging Council, Interventional Council, Surgeons Council, and the HRS Scientific Documents Committee). All information on reviewers RWI was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the governing bodies of the ACC, AHA, and Heart Rhythm Society, and endorsed by the Society of Thoracic Surgery. Page 8 of 56

10 1.4. Scope of the Guideline The task of the 2014 writing committee was to establish revised guidelines for optimum management of AF. The new guideline incorporates new and existing knowledge derived from published clinical trials, basic science, and comprehensive review articles, along with evolving treatment strategies and new drugs. This guideline supersedes the 2006 ACC/AHA/ESC Guideline for the Management of Patients With Atrial Fibrillation (5) and the 2 subsequent focused updates from 2011 (6, 7). In addition, the ACC/AHA, American College of Physicians, and American Academy of Family Physicians submitted a proposal to the Agency for Healthcare Research and Quality to perform a systematic review on specific questions related to the treatment of AF. The data from that report was reviewed by the writing committee and incorporated where appropriate (8). The 2014 AF guideline is organized thematically with recommendations, where appropriate, provided with each section. Some recommendations from earlier guidelines have been eliminated, or updated, as warranted by new evidence or a better understanding of earlier evidence. In developing the 2014 AF guideline, the writing committee reviewed prior published guidelines and related statements. Table 2 is a list of these publications and statements deemed pertinent to this effort and is intended for use as a resource. Table 2. Associated Guidelines and Statements Title Organization Publication Year/ Reference Guidelines Seventh Report of the Joint National Committee on NHLBI 2003 (9) Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Assessment of Cardiovascular Risk in Asymptomatic Adults ACCF/AHA 2010 (10) Coronary Artery Bypass Graft Surgery ACCF/AHA 2011 (11) Hypertrophic Cardiomyopathy ACCF/AHA 2011 (12) Percutaneous Coronary Intervention ACCF/AHA/SCAI 2011 (13) Secondary Prevention and Risk Reduction Therapy for AHA/ACCF 2011 (14) Patients With Coronary and Other Atherosclerotic Vascular Disease Atrial Fibrillation* CCS 2011 (15) Atrial Fibrillation ESC 2012 (16) Device-Based Therapy ACCF/AHA/HRS 2012 (17) Stable Ischemic Heart Disease ACCF/AHA/ACP/ 2012 (18) AATS/PCNA/SCAI/STS Antithrombotic Therapy ACCP 2012 (19) Heart Failure ACCF/AHA 2013 (20) ST-Elevation Myocardial Infarction ACCF/AHA 2013 (21) Non ST-Elevation Acute Coronary Syndromes ACC/AHA 2014 In Press (22) Valvular Heart Disease AHA/ACC 2014 (23) Assessment of Cardiovascular Risk ACC/AHA 2013 (24) Lifestyle Management to Reduce Cardiovascular Risk AHA/ACC 2013 (25) Management of Overweight and Obesity in Adults AHA/ACC/TOS 2013 (26) Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults ACC/AHA 2013 (27) Page 9 of 56

11 Statements Treatment of Atrial Fibrillation AHRQ 2012 (8) Oral Antithrombotic Agents for the Prevention of Stroke in AHA/ASA 2012 (28) Nonvalvular Atrial Fibrillation: a Science Advisory for Healthcare Professionals Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-Up, Definitions, Endpoints, and Research Trial Design HRS/EHRA/ECAS 2012 (29) *Includes the following sections: Catheter Ablation for AF/Atrial Flutter, Prevention and Treatment of AF Following Cardiac Surgery; Rate and Rhythm Management, Prevention of Stroke and Systemic Thromboembolism in AF and Flutter; Management of Recent-Onset AF and Flutter in the Emergency Department; Surgical Therapy; The Use of Antiplatelet Therapy in the Outpatient Setting; and Focused 2012 Update of the CCS AF Guidelines: Recommendations for Stroke Prevention and Rate/Rhythm Control. AATS indicates American Association for Thoracic Surgery; ACC, American College of Cardiology; ACCF, American College of Cardiology Foundation; ACP, American College of Physicians; ACCP, American College of Chest Physicians; AHA, American Heart Association; AHRQ, Agency for Healthcare Research and Quality; ASA, American Stroke Association; AF, atrial fibrillation; CCS, Canadian Cardiology Society; ECAS, European Cardiac Arrhythmia Society; EHRA, European Heart Rhythm Association; ESC, European Society of Cardiology; HRS, Heart Rhythm Society; JNC, Joint National Committee; NHLBI, National Heart, Lung, and Blood Institute; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiac Angiography and Interventions; STS, Society of Thoracic Surgeons, and TOS, The Obesity Society. 2. Clinical Characteristics and Evaluation of AF 2.1. AF Classification AF may be described by the duration of episodes and a simplified scheme revised from the 2006 AF full-text guideline is given in Table 3 (29, 30). Implanted loop recorders, pacemakers, and defibrillators offer the possibility to report frequency, rate, and duration of abnormal atrial rhythms including AF (31, 32). Episodes often increase in frequency and duration over time. Table 3. AF Definitions: A Simplified Scheme Term Definition Paroxysmal AF AF that terminates spontaneously or with intervention within 7 d of onset. Episodes may recur with variable frequency. Persistent AF Continuous AF that is sustained >7 d. Longstanding Continuous AF of >12 mo duration. persistent AF Permanent AF Permanent AF is used when there has been a joint decision by the patient and clinician to cease further attempts to restore and/or maintain sinus rhythm. Acceptance of AF represents a therapeutic attitude on the part of the patient and clinician rather than an inherent pathophysiological attribute of the AF. Acceptance of AF may change as symptoms, the efficacy of therapeutic interventions, and patient and clinician preferences evolve. Page 10 of 56

12 Nonvalvular AF AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. AF indicates atrial fibrillation Mechanisms of AF and Pathophysiology AF occurs when structural and/or electrophysiologic abnormalities alter atrial tissue to promote abnormal impulse formation and/or propagation (Figure 1). These abnormalities are caused by diverse pathophysiologic mechanisms (29, 33, 34), such that AF represents a final common phenotype for multiple disease pathways and mechanisms that are incompletely understood. Figure 1. Mechanisms of AF AF indicates atrial fibrillation; Ca ++ ionized calcium; and RAAS, renin-angiotensin-aldosterone system Risk Factors and Associated Heart Disease Multiple clinical risk factors, electrocardiographic and echocardiographic features, and biochemical makers are associated with an increased risk of AF (Table 4). Page 11 of 56

13 Table 4. Selected Risk Factors and Biomarkers for AF Clinical Risk Factors References Increasing age (35) Hypertension (35) Diabetes mellitus (35) MI (35) VHD (35) HF (35, 36) Obesity (37-39) Obstructive sleep apnea (39) Cardiothoracic surgery (40) Smoking (41) Exercise (42-44) Alcohol use (45-47) Hyperthyroidism (48-50) Increased pulse pressure (51) European ancestry (52) Family history (53) Genetic variants (54-57) Electrocardiographic LVH (58) Echocardiographic LA enlargement (58, 59) Decreased LV fractional shortening (58) Increased LV wall thickness (58) Biomarkers Increased CRP (60, 61) Increased BNP (62, 63) AF indicates atrial fibrillation; BNP, B-type natriuretic peptide; CRP, C-reactive protein; HF, heart failure; LA, left atrial; LV, left ventricular; LVH, left ventricular hypertrophy; MI, myocardial infarction; and VHD, valvular heart disease Clinical Evaluation: Recommendation See Appendix 3 for information on initial clinical evaluation in patients with AF. Class I 1. Electrocardiographic documentation is recommended to establish the diagnosis of AF. (Level of Evidence: C) 3. Thromboembolic Risk and Treatment 3.1. Risk-Based Antithrombotic Therapy: Recommendations See Table 5 for a summary of recommendations from this section. Class I 1. In patients with AF, antithrombotic therapy should be individualized based on shared decisionmaking after discussion of the absolute and RRs of stroke and bleeding, and the patient s values and preferences. (Level of Evidence: C) Page 12 of 56

14 2. Selection of antithrombotic therapy should be based on the risk of thromboembolism irrespective of whether the AF pattern is paroxysmal, persistent, or permanent (64-67). (Level of Evidence: B) 3. In patients with nonvalvular AF, the CHA 2 DS 2 -VASc score is recommended for assessment of stroke risk (68-70). (Level of Evidence: B) 4. For patients with AF who have mechanical heart valves, warfarin is recommended and the target international normalized ratio (INR) intensity (2.0 to 3.0 or 2.5 to 3.5) should be based on the type and location of the prosthesis (71-73). (Level of Evidence: B) 5. For patients with nonvalvular AF with prior stroke, transient ischemic attack (TIA), or a CHA 2 DS 2 -VASc score of 2 or greater, oral anticoagulants are recommended. Options include: warfarin (INR 2.0 to 3.0) (68-70) (Level of Evidence: A), dabigatran (74) (Level of Evidence: B), rivaroxaban (75) (Level of Evidence: B), or apixaban (76). (Level of Evidence: B) 6. Among patients treated with warfarin, the INR should be determined at least weekly during initiation of antithrombotic therapy and at least monthly when anticoagulation (INR in range) is stable (77-79). (Level of Evidence: A) 7. For patients with nonvalvular AF unable to maintain a therapeutic INR level with warfarin, use of a direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban) is recommended. (Level of Evidence: C) 8. Re-evaluation of the need for and choice of antithrombotic therapy at periodic intervals is recommended to reassess stroke and bleeding risks. (Level of Evidence: C) 9. Bridging therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended for patients with AF and a mechanical heart valve undergoing procedures that require interruption of warfarin. Decisions regarding bridging therapy should balance the risks of stroke and bleeding. (Level of Evidence: C) 10. For patients with AF without mechanical heart valves who require interruption of warfarin or newer anticoagulants for procedures, decisions about bridging therapy (LMWH or UFH) should balance the risks of stroke and bleeding and the duration of time a patient will not be anticoagulated. (Level of Evidence: C) 11. Renal function should be evaluated prior to initiation of direct thrombin or factor Xa inhibitors and should be re-evaluated when clinically indicated and at least annually (80-82). (Level of Evidence: B) 12. For patients with atrial flutter, antithrombotic therapy is recommended according to the same risk profile used for AF. (Level of Evidence: C) Class IIa 1. For patients with nonvalvular AF and a CHA 2 DS 2 -VASc score of 0, it is reasonable to omit antithrombotic therapy (80, 81). (Level of Evidence: B) 2. For patients with nonvalvular AF with a CHA 2 DS 2 -VASc score of 2 or greater and who have endstage CKD (creatinine clearance [CrCl] <15 ml/min) or are on hemodialysis, it is reasonable to prescribe warfarin (INR 2.0 to 3.0) for oral anticoagulation (82). (Level of Evidence: B) Class IIb 1. For patients with nonvalvular AF and a CHA 2 DS 2 -VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered. (Level of Evidence: C) 2. For patients with nonvalvular AF and moderate-to-severe CKD with CHA 2 DS 2 -VASc scores of 2 or greater, treatment with reduced doses of direct thrombin or factor Xa inhibitors may be considered (e.g., dabigatran, rivaroxaban, or apixaban), but safety and efficacy have not been established. (Level of Evidence: C) 3. In patients with AF undergoing percutaneous coronary intervention,* bare-metal stents may be considered to minimize the required duration of dual antiplatelet therapy. Anticoagulation may be interrupted at the time of the procedure to reduce the risk of bleeding at the site of peripheral arterial puncture. (Level of Evidence: C) Page 13 of 56

15 4. Following coronary revascularization (percutaneous or surgical) in patients with AF and a CHA 2 DS 2 -VASc score of 2 or greater, it may be reasonable to use clopidogrel (75 mg once daily) concurrently with oral anticoagulants but without aspirin (83). (Level of Evidence: B) Class III: No Benefit 1. The direct thrombin inhibitor, dabigatran, and the factor Xa inhibitor, rivaroxaban, are not recommended in patients with AF and end-stage CKD or on hemodialysis because of the lack of evidence from clinical trials regarding the balance of risks and benefits (74-76, 84-86). (Level of Evidence: C) Class III: Harm 1. The direct thrombin inhibitor, dabigatran, should not be used in patients with AF and a mechanical heart valve (87). (Level of Evidence: B) *See the 2011 percutaneous coronary intervention guideline for type of stent and duration of dual antiplatelet therapy recommendations (13). Table 5. Summary of Recommendations for Prevention of Thromboembolism in Patients With AF Recommendations COR LOE References Antithrombotic therapy based on shared decision-making, discussion of risks of stroke and bleeding, and patient s preferences I C N/A Antithrombotic therapy selection based on risk of thromboembolism I B (64-67) CHA 2 DS 2 -VASc score recommended to assess stroke risk I B (68-70) Warfarin recommended with mechanical heart valves. Target INR intensity should be based on the type and location of prosthesis With prior stroke, TIA, or CHA 2 DS 2 -VASc score 2, oral anticoagulants recommended. Options include: I B (71-73) Warfarin I A (68-70) Dabigatran, rivaroxaban, or apixaban I B (74-76) With warfarin, determine INR at least weekly during initiation and monthly when stable I A (77-79) Direct thrombin or factor Xa inhibitor recommended, if unable to maintain therapeutic INR I C N/A Re-evaluate the need for anticoagulation at periodic intervals I C N/A Bridging therapy with LMWH or UFH recommended with a mechanical heart valve if warfarin is interrupted. Bridging therapy should balance risks of stroke and bleeding I C N/A Without a mechanical heart valve, bridging therapy decisions should balance stroke and bleeding risks against the duration of time patient will I C N/A not be anticoagulated Evaluate renal function prior to initiation of direct thrombin or factor Xa inhibitors, and re-evaluate when clinically indicated and at least annually I B (80-82) For atrial flutter, antithrombotic therapy is recommended as for AF I C N/A With nonvalvular AF and CHA 2 DS 2 -VASc score of 0, it is reasonable to omit antithrombotic therapy IIa B (80, 81) With CHA 2 DS 2 -VASc score 2 and end-stage CKD (CrCl <15 ml/min) or on hemodialysis, it is reasonable to prescribe warfarin for oral anticoagulation IIa B (82) Page 14 of 56

16 With nonvalvular AF and a CHA 2 DS 2 -VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be IIb C N/A considered With moderate-to-severe CKD and CHA 2 DS 2 -VASc scores of 2, reduced doses of direct thrombin or factor Xa inhibitors may be considered IIb C N/A For PCI,* BMS may be considered to minimize duration of DAPT IIb C N/A Following coronary revascularization in patients with CHA 2 DS 2 -VASc score of 2, it may be reasonable to use clopidogrel concurrently with oral anticoagulants, but without aspirin Direct thrombin, dabigatran, and factor Xa inhibitor, rivaroxaban, are not recommended with AF and end-stage CKD or on hemodialysis because of the lack of evidence from clinical trials regarding the balance of risks and benefits Direct thrombin inhibitor, dabigatran, should not be used with a mechanical IIb B (83) III: No Benefit C (74-76, 84-86) III: Harm B (87) heart valve *See the 2011 percutaneous coronary intervention guideline for type of stent and duration of dual antiplatelet therapy recommendations (13). AF indicates atrial fibrillation; BMS, bare-metal stent; CKD, chronic kidney disease; COR, Class of Recommendation; CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; INR, international normalized ratio; LOE, Level of Evidence; LMWH, low-molecular-weight heparin; N/A, not applicable; PCI, percutaneous coronary intervention; TIA, transient ischemic attack; and UFH, unfractionated heparin Risk Stratification Schemes (CHADS 2, CHA 2 DS 2 -VASc, and HAS-BLED) One meta-analysis has stratified ischemic stroke risk among patients with nonvalvular AF using either the AF Investigators (88), the Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism (doubled) (CHADS 2 ) (89), or the Congestive heart failure, Hypertension, Age 75 years (doubled), Diabetes mellitus, Prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65 to74 years, Sex category (CHA 2 DS 2 -VASc) point score systems (Table 6) (16). Table 6. Comparison of the CHADS 2 and CHA 2 DS 2 -VASc Risk Stratification Scores for Subjects With Nonvalvular AF Definition and Scores for CHADS 2 and CHA 2 DS 2 - VASc Score Stroke Risk Stratification With the CHADS 2 and CHA 2 DS 2 -VASc scores Adjusted stroke rate (% per y) CHADS 2 acronym CHADS 2 acronym* Congestive HF % Hypertension % Age 75 y % Diabetes mellitus % Stroke/TIA/TE % Maximum Score % CHA 2 DS 2 -VASc acronym % Congestive HF 1 CHA 2 DS 2 -VASc acronym Hypertension 1 0 0% Age 75 y % Page 15 of 56

17 Diabetes mellitus % Stroke/TIA/TE % Vascular disease (prior MI, PAD, or aortic plaque) % Age y % Sex category (i.e., female sex) % Maximum Score % 8 6.7% % * These adjusted-stroke rates are based on data for hospitalized patients with AF and were published in 2001 (89). Because stroke rates are decreasing, actual stroke rates in contemporary nonhospitalized cohorts might vary from these estimates. Adjusted-stroke rate scores are based on data from Lip and colleagues (90). Actual rates of stroke in contemporary cohorts might vary from these estimates. AF indicates atrial fibrillation; CHADS 2, Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism (doubled); CHA 2 DS 2 -VASc, Congestive heart failure, Hypertension, Age 75 years (doubled), Diabetes mellitus, Prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age years, Sex category; HF, heart failure; LV, left ventricular; MI, myocardial infarction; PAD, peripheral artery disease; TE, thromboembolic; and TIA, transient ischemic attack (90, 91) Considerations in Selecting Anticoagulants For patients with CKD, dose modifications of the new agents are available (Table 7); however, for those with severe or end-stage CKD, warfarin remains the anticoagulant of choice, as there are no or very limited data for these patients. Among patients on hemodialysis, warfarin has been used with acceptable risks of hemorrhage (82). Table 7. Dose Selection of Oral Anticoagulant Options for Patients with Nonvalvular AF and CKD (Based on Prescribing Information for the United States)* Renal Function Warfarin (92) Dabigatran (74) Rivaroxaban (75) Apixaban (76) Normal/Mild Impairment Moderate Impairment Severe Impairment End-Stage CKD Not on Dialysis End-Stage CKD on Dialysis Dose adjusted for INR Dose adjusted for INR Dose adjusted for INR mg BID (CrCl >30 ml/min) 150 mg BID or 75 mg BID (CrCl >30 ml/min) 75 mg BID (CrCl ml/min) 20 mg QD with the evening meal (CrCl >50 ml/min) 15 mg QD with the evening meal (CrCl ml/min) 15 mg QD with the evening meal (CrCl ml/min) Not recommended (CrCl <15 ml/min) 5.0 or 2.5 mg BID 5.0 or 2.5 mg BID No recommendation, See section Dose adjusted for INR Dose adjusted for INR Not recommended (CrCl <15 ml/min) Not recommended (CrCl <15 ml/min) Not recommended (CrCl <15 ml/min) No recommendation, See section No recommendation, See section # *Renal function should be evaluated prior to initiation of direct thrombin or factor Xa inhibitors and should be reevaluated when clinically indicated and at least annually. CrCl should be measured using the Crockoft-Gault method. The concomitant use of P-glycoprotein inducers or inhibitors with dabigatran, or the concomitant use of dual P- glycoprotein and strong CYP3A4 inducers or inhibitors with either rivaroxaban or apixaban, particularly in the setting of CKD, may require dosing adjustment or avoidance of concomitant drug use (see the FDA drug label at Section 8.6). Page 16 of 56

18 Use apixaban 2.5 mg BID if any 2 patient characteristics present: Cr 1.5 mg/dl, 80 years of age, body weight 60 kg (76). Apixaban is not recommended in patients with severe hepatic impairment. Modeling studies suggest that dabigatran 75 mg BID might be safe for patients with CrCl 15 30mL/min, but this has not been validated in a prospective cohort. Some countries outside the United States use 110 mg BID (74). Dose-adjusted warfarin has been used, but observational data regarding safety and efficacy are conflicting. No published studies support a dose for this level of renal function. #In patients with end-stage CKD on stable hemodialysis, prescribing information indicates the use of apixaban 5 mg BID with dose reduction to 2.5 mg BID if the patient is either 80 years of age or body weight 60 kg. AF indicates atrial fibrillation; BID, twice daily; CKD, chronic kidney disease; Cr, creatinine; CrCl, creatinine clearance; INR, international normalized ratio; and QD, once daily Cardiac Surgery LAA Occlusion/Excision: Recommendation Class IIb 1. Surgical excision of the LAA may be considered in patients undergoing cardiac surgery. (Level of Evidence: C) 4. Rate Control: Recommendations See Table 8 for a summary of recommendations for this section and Table 9 for AF rate control common medication dosages. Class I 1. Control of the ventricular rate using a beta blocker or nondihydropyridine calcium channel antagonist is recommended for patients with paroxysmal, persistent, or permanent AF (93-95). (Level of Evidence: B) 2. Intravenous administration of a beta blocker or nondihydropyridine calcium channel blocker is recommended to slow the ventricular heart rate in the acute setting in patients without preexcitation. In hemodynamically unstable patients, electrical cardioversion is indicated (96-99). (Level of Evidence: B) 3. In patients who experience AF-related symptoms during activity, the adequacy of heart rate control should be assessed during exertion, adjusting pharmacological treatment as necessary to keep the ventricular rate within the physiological range. (Level of Evidence: C) Class IIa 1. A heart rate control (resting heart rate <80 bpm) strategy is reasonable for symptomatic management of AF (95, 100). (Level of Evidence: B) 2. Intravenous amiodarone can be useful for rate control in critically ill patients without preexcitation ( ). (Level of Evidence: B) 3. AV nodal ablation with permanent ventricular pacing is reasonable to control the heart rate when pharmacological therapy is inadequate and rhythm control is not achievable ( ). (Level of Evidence: B) Class IIb 1. A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable as long as patients remain asymptomatic and LV systolic function is preserved (100). (Level of Evidence: B) 2. Oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or contraindicated. (Level of Evidence: C) Class III: Harm Page 17 of 56

19 1. AV nodal ablation with permanent ventricular pacing should not be performed to improve rate control without prior attempts to achieve rate control with medications. (Level of Evidence: C) 2. Nondihydropyridine calcium channel antagonists should not be used in patients with decompensated HF as these may lead to further hemodynamic compromise. (Level of Evidence: C) 3. In patients with pre-excitation and AF, digoxin, nondihydropyridine calcium channel antagonists, or intravenous amiodarone should not be administered as they may increase the ventricular response and may result in ventricular fibrillation (107). (Level of Evidence: B) 4. Dronedarone should not be used to control the ventricular rate in patients with permanent AF as it increases the risk of the combined endpoint of stroke, MI, systemic embolism, or cardiovascular death (108, 109). (Level of Evidence: B) Table 8. Summary of Recommendations for Rate Control Recommendations COR LOE References Control ventricular rate using a beta blocker or nondihydropyridine calcium channel antagonist for paroxysmal, persistent, or permanent AF I B (93-95) IV beta blockers or nondihydropyridine calcium channel blocker recommended to slow ventricular heart rate in the acute setting in patients without pre-excitation. In hemodynamically unstable patients, electrical I B (96-99) cardioversion is indicated For AF, assess heart rate control during exertion, adjusting pharmacological treatment as necessary I C N/A A heart rate control (resting heart rate <80 bpm) strategy is reasonable for symptomatic management of AF IIa B (95, 100) IV amiodarone can be useful for rate control in critically ill patients without pre-excitation IIa B ( ) AV nodal ablation with permanent ventricular pacing is reasonable when pharmacological management is inadequate and rhythm control is not IIa B ( ) achievable Lenient rate control strategy (resting heart rate <110 bpm) may be reasonable with asymptomatic patients and LV systolic function is preserved IIb B (100) Oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or contraindicated IIb C N/A AV nodal ablation should not be performed without prior attempts to achieve rate control with medications III: Harm C N/A Nondihydropyridine calcium channel antagonists should not be used in decompensated HF III: Harm C N/A With pre-excitation and AF, digoxin, nondihydropyridine calcium channel antagonists, or amiodarone, should not be administered III: Harm B (107) Dronedarone should not be used to control ventricular rate with permanent AF III: Harm B (108, 109) AF indicates atrial fibrillation; AV, atrioventricular; COR, Class of Recommendation; HF, heart failure; IV, intravenous; LOE, Level of Evidence; LV, left ventricular; and N/A, not applicable. Table 9. AF Rate Control Common Medication Dosage Intravenous Administration Usual Oral Maintenance Dose Beta blockers Metoprolol tartrate mg IV bolus over 2 min; up to 3 doses mg BID Metoprolol XL (succinate) N/A mg QD Page 18 of 56

20 Atenolol N/A mg QD Esmolol 500 mcg/kg IV bolus over 1 min, then mcg/kg/min IV Propranolol 1 mg IV over 1 min, up to 3 doses at 2 min intervals mg TID or QID Nadolol N/A mg QD Carvedilol N/A mg BID Bisoprolol N/A mg QD Nondihydropyridine calcium channel antagonists Verapamil ( mg/kg) IV bolus over 2 min, may give an additional 10.0 mg after 30 min if no response, then mg/kg/min infusion N/A mg QD (ER) Diltiazem 0.25 mg/kg IV bolus over 2 min, then 5-15 mg/h mg QD (ER) Digitalis glycosides Digoxin 0.25 mg IV with repeat dosing to a maximum of 1.5 mg over 24 h mg QD Others Amiodarone 300 mg IV over 1 h, then mg/h over 24 h mg QD AF indicates atrial fibrillation; BID, twice daily; ER, extended release; IV, intravenous; N/A, not applicable; QD, once daily; QID, four times a day; and TID, three times a day. 5. Rhythm Control See Table 10 for a summary of recommendations from this section Thromboembolism Prevention: Recommendations Class I 1. For patients with AF or atrial flutter of 48-hour duration or longer, or when the duration of AF is unknown, anticoagulation with warfarin (INR 2.0 to 3.0) is recommended for at least 3 weeks prior to and 4 weeks after cardioversion, regardless of the CHA 2 DS 2 -VASc score and the method (electrical or pharmacological) used to restore sinus rhythm ( ). (Level of Evidence: B) 2. For patients with AF or atrial flutter of more than 48 hours or unknown duration that requires immediate cardioversion for hemodynamic instability, anticoagulation should be initiated as soon as possible and continued for at least 4 weeks after cardioversion unless contraindicated. (Level of Evidence: C) 3. For patients with AF or atrial flutter of less than 48-hour duration and with high risk of stroke, intravenous heparin or LMWH, or administration of a factor Xa or direct thrombin inhibitor, is recommended as soon as possible before or immediately after cardioversion, followed by longterm anticoagulation therapy. (Level of Evidence: C) 4. Following cardioversion for AF of any duration, the decision regarding long-term anticoagulation therapy should be based on the thromboembolic risk profile (Section 4). (Level of Evidence: C) Class IIa 1. For patients with AF or atrial flutter of 48-hour duration or longer or of unknown duration who have not been anticoagulated for the preceding 3 weeks, it is reasonable to perform a TEE prior to cardioversion and proceed with cardioversion if no LA thrombus is identified, including in the LAA, provided that anticoagulation is achieved before TEE and maintained after cardioversion for at least 4 weeks (114). (Level of Evidence: B) Page 19 of 56